MAnorm2 Tools for Normalizing and Comparing ChIP-seq Samples

Eukaryotic gene transcription is regulated by a large cohort of chromatin associated proteins, and inferring their differential binding sites between cellular contexts requires a rigorous comparison of the corresponding ChIP-seq samples. The package MAnorm2 is primarily developed for quantitatively comparing groups of ChIP-seq samples (e.g., groups of biological replicates corresponding to different cellular contexts). Technically, MAnorm2 uses a hierarchical strategy for normalization of ChIP-seq samples, and it assesses within-group variability of ChIP-seq signals under an empirical Bayes framework, in which MAnorm2 considers the abundance of differential ChIP-seq signals between groups of samples and the possibility of different within-group variability between groups. Another capability of MAnorm2 is to identify hypervariable ChIP-seq signals across samples, which, for example, is essential to dissecting the epigenetic heterogeneity across cancer patients as well as revealing potential sub-structures associated with them.